Α-synuclein induces microglial cell migration through stimulating HIF-1α accumulation.

Abstract

Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α-synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α-synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague-Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 μM) of α-synuclein oligomers. The mRNA and protein levels of HIF-1α were then analyzed by qRT-PCR and Western blot. Cell migration was examined by a 96-well Boyden chamber. Moreover, toll-like receptor (TLR) 2-expression as well as TLR7/8-expression was inhibited by specific siRNA transfection. HIF-1α was overexpressed by Ad-HIF-1α transfection. In the results, α-synuclein was found to stimulate HIF-1α accumulation in microglial cells in a dose-dependent manner. Silencing HIF-1α expression dampened α-synuclein induced microglial cell migration. Furthermore, blockade of TLR7/8 expression but not TLR2 expression reduced HIF-1α accumulation in microglial cells. In addition, overexpressed HIF-1α, along with Src, prompted caveolin-1 expression and phosphorylation, as well as migration in microglial cells. Α-synuclein acts via TLR7/8 and enhances HIF-1α expression, which might play a regulatory role in microglial cell migration. © 2017 Wiley Periodicals, Inc.